The present invention relates to a process of preparing grafts for biological dressing, such as applied in the case of burns, wounds, ulcers, and removal of patches of skin in such a manner as to overcome histocompatibility barriers, and so as to make possible grafts which have a long, effective duration in the recipient, and which have increased resistance to infection and are substantially devoid of undesired effects on the recipient.
The main obstacle encountered in organ transplantation is the immune rejection of the transplant. The rejection phenomenon originates from antigenic differences between the cells of the recipient and the transplant, as well as from the natural immune response of the organism towards "non-self" antigens. Attempts to prolong the survival of allografts and xenografts, both in experimental models and in medical practice, have been mainly aimed at the supression of the immune apparatus of the recipient. This has been achieved by means of cytotoxic drugs, antimetabolites, corticosteroids and antilymphocytic serum. The generalized immunosuppression, however, is accompanied by undesirable toxic effects, decreased resistance to infection and reduction in the level of the haemopoietic stem cells. Another possibility is to attenuate, or to abolish completely, the antigenicity of the graft with preservation of its biological functions. The advantage of this approach is that the immune capacity of the recipient is not affected. Investigations along this line, have been, for the most part, unsuccessful. Most studies were performed with animals and only recently it has been subjected to clinical evaluation. Using laboratory animals, the treatment of allografts or xenografts in vitro, with cortisone, thalidomide or urethane prolonged their retention time by a factor of about two. The amount of drug locally applied to the skin was smaller than the amount required to achieve a similar effect by injecting the drug systemically. In attempts to modify the antigenic properties of grafts, the donor skin has been treated in vitro with streptokinase/streptodornase, or with RNA and DNA preparations of the recipient. Allograft survival was not prolonged by exposure of donor skin to transplantation antigens of the recipient. Minimal immune reaction was observed towards grafts in which cellular viability was destroyed in vitro treatment with formalin or cyanide or by freeze-drying. The majority of the dead grafts were retained by the host for a limited period of time.
Blood vessel xenografts treated by 1% solution of the enzyme ficin, then treated by 1.3% solution of dialdehyde starch for 18 hours, and stored in a solution containing 50% ethanol and 1% propylene oxide for sterility, were tested in experimental animals, and have been recently used clinically to replace damaged blood vessels. In the last few years freeze dried pig-skin xenografts have been used as temporary dressing in the treatment of burns. These dressings exhibit minimal or no antigenicity, but it is necessary to replace the freeze dried pig-skin dressing every 2-4 days before they become adherent and infected.